Alzheimer's Disease Investigated via Gene-Environment Interactions, Biochemical Pathways, Cellular Processes, and Disease Phenotype Variability DOI Creative Commons
Viqas Shafi,

Ifrah Siddiqui

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Abstract Background: Alzheimer's disease (AD) is a neurodegenerative disorder influenced by genetic and environmental factors. APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, CD33 play key roles in AD pathogenesis, affecting biochemical pathways cellular processes. However, the interaction between predisposition factors, as well reasons for variability phenotype, remain poorly understood. This study aims to investigate these interactions improve our understanding of etiology inform personalized interventions. Methods: A comprehensive search encompassing databases such PubMed, MEDLINE, Google Scholar, open access/subscription-based journals was conducted retrieve relevant articles investigation genes involved including CD33. Articles were searched without any date restrictions. Utilizing criteria delineated methodology section, studies systematically reviewed elucidate how factors genetics influence onset, progression, symptom severity, progression rates. adheres PRISMA guidelines (Preferred Reporting Items Systematic Reviews Meta-Analyses). Results: Our revealed complicated predisposition, pathways, processes pathogenesis. amyloid-beta production, tau pathology, lipid metabolism, inflammation AD. These interact with diet, pollutants, head trauma, lifestyle, modulating risk progression. Additionally, we found phenotype among individuals carrying similar mutations, modifiers, cognitive reserve, neurobiological differences. Conclusion: multifactorial critical pathogenesis inflammation. further Understanding essential developing interventions delay reduce slow

Language: Английский

Meroterpenoids from Terrestrial and Marine Fungi: Promising Agents for Neurodegenerative Disorders—An Updated Review DOI Creative Commons

Daniela S. Dimitrova,

Simeonka Dimitrova,

Gabriela Kehayova

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 96 - 96

Published: Feb. 3, 2025

Background: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because their wide range biological activities, such as anti-cholinesterase, COX-2 inhibitory, antibacterial, antiviral, antidiabetic, antioxidant, anti-inflammatory, antineoplastic, and cardioprotective properties. This review aims to consolidate recognized neuroprotective effects meroterpenoids from marine terrestrial fungi. Methods: Data compiled several databases, including PubMed, Science Direct, Scopus, Google Scholar, include articles published since 2000 using keywords “neuroprotective”, “fungi”, “mushroom”, “marine sponge”, “neurodegeneration”, “dementia” in connection with “meroterpenoids”. Results: modulate different cell signaling pathways exhibit often combined mechanisms action ameliorate neuronal damage dysfunction. Reported activities BACE1 inhibition, anti-inflammatory all potential treatment dementia associated neurodegenerative diseases Alzheimer’s Parkinson’s. Conclusions: be developed effective tools for neuropathological diseases. Ongoing research elucidate various remains essential requires further investigation.

Language: Английский

Citations

0
Mechanisms of the Pathogenesis of Alzheimer’s Disease: The Role of the Basal Forebrain DOI
Valentina Kitchigina, I. Yu. Popova, Liubov Shubina

et al.

Neuroscience and Behavioral Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

Citations

0
Implications of Mucin-Type O-Glycosylation in Alzheimer’s Disease DOI Creative Commons

N. Navarro,

Gustavo De Nadai Mundim, Mare Čudić

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(9), P. 1895 - 1895

Published: April 24, 2025

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders linked to aging. Major hallmarks AD pathogenesis include amyloid-β peptide (Aβ) plaques, which are extracellular deposits originating from processing amyloid precursor protein (APP), and neurofibrillary tangles (NFTs), intracellular aggregates tau protein. Recent evidence indicates that disruptions in metal homeostasis impaired immune recognition these trigger neuroinflammation, ultimately driving progression. Therefore, a more comprehensive approach needed understand underlying causes disease. Patients with present abnormal glycan profiles, known AD-related molecules either modified glycans or involved regulation. A deeper understanding how O-glycosylation influences balance between amyloid-beta production clearance, as well microglia’s pro- anti-inflammatory responses, crucial for deciphering early pathogenic events AD. This review aims provide summary extensive research conducted on role mucin-type AD, discussing its onset recognition.

Language: Английский

Citations

0
Revolutionizing neurotherapeutics: Nanocarriers unveiling the potential of phytochemicals in Alzheimer's disease DOI Creative Commons
Akshatha Kamath, Pawan G. Nayak, Jeena John

et al.

Neuropharmacology, Journal Year: 2024, Volume and Issue: 259, P. 110096 - 110096

Published: July 29, 2024

Neurological disorders pose a huge worldwide challenge to the healthcare system, necessitating innovative strategies for targeted drug delivery central nervous system. Alzheimer's disease (AD) is an untreatable neurodegenerative condition characterized by dementia and alterations in patient's physiological mental states. Since ancient times, medicinal plants have been important source of bioactive phytochemicals with immense therapeutic potential. This review investigates new safer alternatives prevention treatment related inevitable side effects associated synthetic compounds. examines how nanotechnology can help enhancing neuroprotective AD. Nevertheless, despite their remarkable properties, these natural products often poor efficacy due low bioavailability, limited solubility imperfect blood brain barrier (BBB) penetration. Nanotechnology produces personalized systems which are necessary solving such problems. In overcoming challenges, might be employed as way forward whereby customized medication would established result. The use nanocarriers design application highlighted this review, indicate potential revolutionizing delivery. We also explore complications possibilities using supply nutraceuticals improve patients' standard living, preclinical well clinical investigations displaying that techniques effective mitigating diseases. order fight diseases health, scientists doctors employ its possible interventions.

Language: Английский

Citations

3
Exploring the multiple therapeutic mechanisms and challenges of mesenchymal stem cell-derived exosomes in Alzheimer's disease DOI Open Access
Yanan Ma,

Xiqi Hu,

Kenji Karako

et al.

BioScience Trends, Journal Year: 2024, Volume and Issue: 18(5), P. 413 - 430

Published: Oct. 10, 2024

Alzheimer's disease (AD) is a severe neurodegenerative disorder, and the current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exos) have garnered significant attention due to their unique biological properties, showcasing tremendous potential as an acellular alternative therapy for AD. MSC-Exos exhibit excellent biocompatibility low immunogenicity, enabling them effectively cross blood-brain barrier (BBB) deliver therapeutic molecules directly target cells. They highly efficacious in delivering nucleic acid-based drugs. Moreover, production process of benefits from high proliferation capacity multilineage differentiation potential, allowing while maintaining stable composition. Despite theoretical advantages MSC-Exos, clinical use still faces multiple challenges, including cross-contamination during isolation purification processes, complexity components, presence adverse paracrine factors. Future research needs focus on optimizing separation techniques, enhancing delivery methods improve efficacy, performing detailed analyses components MSC-Exos. In summary, hold promise effective option AD other diseases, driving related fields.

Language: Английский

Citations

3
Organophosphate Insecticide Malathion Induces Alzheimer’s Disease-Like Cognitive Impairment in Mice: Evidence of the Microbiota-Gut-Brain Axis DOI

Jingna Cui,

Shouchun Xiao,

Yue Cao

et al.

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Evidence suggests that exposure to organophosphate pesticides increases the risk of neurodegenerative diseases, but mechanisms remain unclear. This study investigated effects malathion on Alzheimer's disease (AD)-like symptoms at environmentally relevant concentrations using wild-type (WT) and APP/PS1 transgenic mouse models. Results showed induced AD-like cognitive impairment, amyloid-β (Aβ) accumulation, neuroinflammation in WT mice, with worsened mice. Mechanistic studies revealed gut microbiota dysbiosis (reduced Lactobacillus Akkermansia, increased Dubosiella), causing barrier impairment tryptophan metabolism disruptions. resulted a significant increase indole derivatives activation colonic aryl hydrocarbon receptor (AhR), promoting kynurenine (KYN) pathway while inhibiting serotonin (5-HT) pathway. Increased neurotoxic KYN metabolites (3-hydroxykynurenine quinolinic acid) triggered systemic inflammation, upregulating hippocampal IL-6 IL-1β mRNA levels thereby neuroinflammation. Gut disruptions caused neurotransmitter imbalances, reducing 5-HT its derivatives. These promoted AD progression both highlights crucial role microbiota-gut-brain axis by exposure, providing insights into risks posed pesticides.

Language: Английский

Citations

3
Understanding the Molecular Impact of Physical Exercise on Alzheimer’s Disease DOI Open Access

Alba Cantón-Suárez,

Leticia Sánchez-Valdeón, Laura Bello-Corral

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13576 - 13576

Published: Dec. 18, 2024

Alzheimer’s disease is one of the most common neurodegenerative diseases, characterized by a wide range neurological symptoms that begin with personality changes and psychiatric symptoms, progress to mild cognitive impairment, eventually lead dementia. Physical exercise part non-pharmacological treatments used in disease, as it has been shown delay process improving redox state brain tissue, providing anti-inflammatory effects or stimulating release brain-derived neurotrophic factor enhances structure performance. Here, we reviewed results obtained from studies conducted both animal models human subjects comprehend how physical interventions can exert molecular mechanisms underlying pathophysiological processes disease: amyloid β-peptide pathology, tau neuroglial changes, mitochondrial dysfunction, oxidative stress. seems have protective effect against since induce positive some biomarkers related disease. However, additional humans are necessary address current lack conclusive evidence.

Language: Английский

Citations

2
Implications of liquid-liquid phase separation and ferroptosis in Alzheimer's disease DOI
Fu-Wei Wang, Zihao Chen, Qiong Zhou

et al.

Neuropharmacology, Journal Year: 2024, Volume and Issue: 259, P. 110083 - 110083

Published: July 21, 2024

Language: Английский

Citations

1
Targeting Protein Aggregation: the Promising Application of Polyoxometalates in Neurodegenerative Diseases DOI
Junyi Chen,

Wenzhu Yang,

Huilan Chen

et al.

Inorganic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Recent progress in the therapeutic applications of polyoxometalates (POMs) to target protein aggregates neurodegenerative diseases (NDDs) is reviewed.

Language: Английский

Citations

1
Mechanism of Metal Complexes in Alzheimer’s Disease DOI Open Access

Yi LIU,

Jiaying Ma,

Qianling Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11873 - 11873

Published: Nov. 5, 2024

Alzheimer's disease (AD) is a kind of neurodegenerative diseases characterized by beta-amyloid deposition and neurofibrillary tangles also the main cause dementia. According to statistics, incidence AD constantly increasing, bringing great burden individuals society. Nonetheless, there no cure for AD, available drugs are very limited apart from cholinesterase inhibitors N-Methyl-D-aspartic acid (NMDA) antagonists, which merely alleviate symptoms without delaying progression disease. Therefore, an urgent need develop medicine that can delay or it. In recent years, increasing evidence suggests metal complexes have enormous potential treat through inhibiting aggregation cytotoxicity Aβ, interfering with congregation hyperphosphorylation tau, regulating dysfunctional synaptic unbalanced neurotransmitters, etc. this review, we summarize current their mechanisms action treating including ruthenium, platinum, zinc, vanadium, copper, magnesium, other complexes.

Language: Английский

Citations

1